GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR ENHANCES EBV-INDUCEDSYNTHESIS OF CHEMOTACTIC FACTORS IN HUMAN NEUTROPHILS

We have recently demonstrated that EBV binds to human neutrophils and stimulates a wide range of activities, including homeotypic aggregatio n, total RNA synthesis, and expression of the chemokines IL-8 and macr ophage Inflammatory protein-1 alpha (MIP-1 alpha). Neutrophil function is also known to be modulated by priming with granulocyte-macrophage colony-stimulating factor (GM-CSF). We have therefore investigated the modulation of EBV-induced activation of human neutrophils by GM-CSF. Treatment of neutrophils with GM-CSF before EBV activation enhanced th e production of both MIP-1 alpha and IL-8. The IL-8 produced under the se conditions was biologically active as determined in the calcium mob ilization assay. GM-CSF was also found to increase the ability of EBV to prime neutrophils for increased leukotriene B-4 (LTB4) synthesis. P rior treatment of GM-CSF with neutralizing Abs inhibited these effects . GM-CSF also increased the specific binding of FITC-EBV to the neutro phil surface, as evaluated by fluorocytometry. Local production of GM- CSF in tissues invaded by EBV could therefore serve to potentiate a ho st defense mechanism directed toward the destruction of the infectious virus via increased production of chemotactic factors, Since both IL- 8 and MIP-1 alpha are reported to be chemoattractants in vitro for T c ells and T and B cells, respectively, the ability of EBV to induce the ir production by neutrophils may enhance its ability to infect B and T lymphocytes via increased recruitment to sites of infection.